Molecular response to imatinib in patients with chronic myeloid leukemia in Tanzania

Abstract

ABSTRACT Imatinib is the mainstay of treatment of patients with chronic myeloid leukemia (CML) in Tanzania. Monitoring molecular response to therapy by real-time polymerase chain reaction at defined milestones is necessary for early detection of treatment failure. However, this assay is not routinely performed in Tanzania; therefore, the depth of molecular response among patients with CML is not known. A total of 158 patients with previously diagnosed CML who received imatinib treatment were recruited from January 2019 and followed up through October 2020 at Ocean Road Cancer Institute. Information was obtained at the time of diagnosis and follow-up. Blood samples were collected in EDTA tubes to measure the BCR/ABL ratio on the Gene Xpert system for molecular response determination. The median age of the 158 adult patients was 45 years (range, 18-86). By reference to established treatment milestones, only 37 (23.4%) achieved optimal molecular response. Signs of advanced-stage disease, in particular the need for red cell transfusions before diagnosis (adjusted odds ratio [AOR], 3.4; 95% CI, and 1.32-9.17) and cytopenias (AOR, 2.26; 95% CI, and 1.03-4.96) necessitating drug interruptions were statistically validated predictors of treatment failure on multivariate, multinomial logistic regression. Patient survival at the 22-month follow-up was lowest, with 78.6% (95% CI, 69.4-85.4) in the failure-to-respond category and highest in patients achieving optimal response 97.0% (95% CI, 80.9-99.6). In summary, the majority of patients with CML treated with imatinib in Tanzania do not obtain deep molecular response. This outcome can be attributed to late diagnosis, the development of cytopenias requiring multiple drug interruptions, and poor adherence to treatment. Methods, Study population: Previously diagnosed patients with CML were recruited from January 2019 and followed up through October 2020 at the CML day clinic at ORCI in Tanzania. Diagnosis of CML was established by examination of peripheral blood and bone marrow and confirmed by PCR for the BCR-ABL fusion gene. The PCR test was carried out in all patients to fulfill a requirement for access to free imatinib under the GIPAP. Eligible patients were adults aged ≥18 years who had been receiving imatinib treatment for at least 3 months. Excluded were patients with newly diagnosed disease receiving imatinib treatment for <3 months, or receiving TKIs other than imatinib, or undergoing cytoreduction with hydroxyurea. Results: Of 191 patients attending the Ocean Road CML Clinic from January through May 2019, 33 were not eligible: 14 were <18 years of age, 15 had been receiving imatinib for <3 months, 3 were on the second line of TKIs, and 1 had undergone a hematopoietic stem cell transplant in India. Thus, 158 patients were recruited into the study after they provided informed written consent. Among those, 104 patients had data available for Sokal score calculation, and 132 had data available to determine the CML clinical phase.